Circular RNA circBACH2 plays a role in papillary thyroid carcinoma by sponging miR-139-5p and regulating LMO4 expression

Abstract

Circular RNAs (circRNAs) are a class of non-coding RNAs that are broadly expressed in various biological cells and function in regulating gene expression. They are structurally stable and tissue-specific. However, the function of human circRNAs and the role of circRNAs in papillary thyroid carcinoma (PTC) remain to be determined. Herein, the function of circRNA circBACH2 was investigated in human PTC cells. First, we detected the expression of circBACH2 in PTC tissues and PTC cell lines by RT-PCR. FISH was used to confirm the subcellular localization of circBACH2. A luciferase reporter assay and AGO2-RIP was used to confirm the relationship between circBACH2 and miR-139-5p. PTC cells were stably transfected with siRNA against circBACH2 and cell proliferation, migration and invasion were detected to evaluate the effect of circBACH2 in PTC, while tumorigenesis was assayed in nude mice. We found that circBACH2 was highly expressed in PTC tissues and PTC cell lines. Mechanistically, we confirmed that circBACH2 could directly bind to miR-139-5p and relieve suppression of the target LMO4. Functionally, we found that inhibiting circBACH2 expression decreased cell proliferation, migration, and invasion. Finally, down-regulating circBACH2 suppressed the growth of PTC xenografts in nude mice. Our findings indicate that circBACH2 acts as a novel oncogenic RNA that sponges miR-139-5p and can be used as a tumor biomarker of PTC. What’s more, these results revealed that the circBACH2/miR-139-5p/LMO4 axis could be targeted as a potential treatment strategy for PTC.

Progression Risk Assessment of Post-Surgical Papillary Thyroid Carcinoma Based on Circular RNA-Associated Competing Endogenous RNA Mechanisms

“…hsa-miR-139-5p was identi ed to be downregulated in the primary tumor and further in PTC metastasis [44]. hsa-miR-139-5p was also able to be sponged by circBACH2 and relieved the suppression of the target gene LMO4 in PTC [45]. RIMS2 was identi ed as a novel target of hsa-miR-139-5p in this study.…”

CircRNA LRIG3 knockdown inhibits the progression of hepatocellular carcinoma by regulating miR-223-3p/MAP2K6 axis and inactivating MAPK/ERK pathway

“…In addition, because of their covalently closed-structure, circRNAs are more stable and more suitable as efficacious biomarkers than linear-RNAs, such as lncRNAs and miRNAs [20]. For instance, circ_UVRAG [21], circ_BACH2 [22] and circ_ANKS1B [23] have been identified to be diagnostic or prognostic biomarker for gastric cancer, papillary thyroid carcinoma and breast cancer, respectively. Previous report has been demonstrated that hsa_circ_0027345 (a circRNA derived from linear LRIG3) was overexpressed in HCC tissues [11].…”

<p>Biological Roles and Mechanisms of Circular RNA in Human Cancers</p>

“…Therefore, circBACH2/miR-139-5p/LMO4 regulatory axis could be a promising treatment strategy for PTC patients. 172 Likewise, low expression of circRAPGEF5 plays an important role in suppressing the aggressive biological behaviors of PTC by sponging miR-198, this subsequently downregulated the expression of fibroblast growth factor receptor 1 (FGFR1), a target gene of miR-198. 173 Moreover, overexpression of circ_0025033 promoted proliferation and invasion of PTC by directly sponging miR-1231 and miR-1304, therefore, circ_0025033/miR-1231/miR-1304 signaling pathway was considered to be a new regulatory mechanism in PTC initiation and progression.…”